The two major products secreted by the stomach, hydrochloric acid and pepsin (a protease), both participate in protein digestion. Hydrochloric acid helps dissolve the particulate matter in food and provides an optimal pH for the activity of pepsin. Frequent occurrence of elevated levels of gastric acid and pepsin can lead to aggravation of the lining of the stomach resulting in digestion of the mucosal cells and leading to peptic ulcers Peptic ulcers are perforations in the mucous membrane where the lining of the stomach (gastric ulcers) or duodenum (duodenal ulcers) is exposed to the acidic contents of the stomach. When gastric hydrochloric acid reaches the exposed nerve in the ulcers they signal pain to the central nervous system. The gastric acid may also cause ulcers in the oesophagus.
Antacids relieve the symptoms of peptic ulcers by performing a neutralization reaction, i.e. they buffer gastric acid, raising the pH to reduce acidity in the stomach. Antacids also relieve heartburn (hydrochloric acid from the stomach entering into the oesophagus). Hydrotalcite (MgAl) antacids have also been reported by Playle et al to relieve symptoms by inhibiting pepsin activity and are also believed to provide mucosal protection by its ability to mimic the properties of the gastric mucus gel.
Examples of antacids are Al(OH)3, Mg(OH)2, Ca Carbonate, and MgAl hydrotalcite. Although effective, antacids may give rise to new problems.
Some antacids are known to stop digestion of protein in the stomach by raising the pH to above 7, which may irreversibly inactivate pepsin. Undigested protein in the GI tract can then cause a multitude of problems including gas, bloating and constipation. The presence of food may also increase the gastric pH and levels of gastrin, consequently the combination of food and certain types of antacid may lead to a sudden increase in the gastric pH above 7 before the stomach empties and the pH decreases again. It is desirable that a compound used in the treatment of gastric ulcer should not only be an effective acid buffering agent, but should also avoid sudden changes in gastric pH. Furthermore, an antacid should inhibit pepsin but not too much so that pepsin may be irreversibly inactivated.
A further problem of antacids is that they may cause an ‘acid rebound effect’ because a ‘biological switch’ or feedback mechanism exists in the stomach. For example, if the gastric pH is at a high pH value then the hormone gastrin is stimulated which in turn stimulates further acid secretion in which the gastric acid returns in greater concentration. Consequently, this may lead a positive feed-back loop and thus requiring further use of antacids. This is associated with antacids with the most rapid onset of action whereby the pH is suddenly increased to a higher pH value (typically above pH 5).
It is also known that excess acid (typically below pH 3) can aggravate ulcers; pain can occur when the acid irritates the exposed nerves in the ulcers. Consequently, the optimum range to which antacids should buffer gastric pH is between pH 3-4.5 when taken without food and should not exceed pH 7 in the presence of food.
Particular antacids are also known to cause problems                Magnesium hydroxides has laxative properties, may release significant amounts of magnesium and can lead to sudden changes to higher gastric pH values (ie above pH 7).        Regular doses of high levels of carbonates (typically generated by some carbonate-based antacids such as Ca carbonate) may cause alkalosis.        MgFe or MgAl hydrotalcites may contain carbonate but typically at lower level (<100 g CO3/kg) than contained in CaCO3 (600 g CO3/kg) or MgCO3 (710 g CO3/kg)        MgAl hydrotalcites are believed to avoid the acid rebound effect and have been reported to provide mucosal protection. However, the absorption of Al3+ from antacids based on aluminium is a concern. This may result in Al accumulation in the body to toxic levels.        Some antacids have high sodium content and should be avoided by those on a low sodium diet.        
Hydrotalcite-type materials may be preferred as they have a dual action. It is hypothesised that stomach acid reacts rapidly with hydrotalcite via anion exchange neutralisation to yield the chloride form of the compound. The mineral then further reacts with physiological fluid to slowly disintegrate the mineral skeleton thereby providing long term buffering. This dual action results in a compound providing rapid relief from acute indigestion, and the prolonged action required for recurring dyspepsia.
An increase in surface area of either the hydrotalcite-crystallites or -particles would be expected to cause an increase in rate of reaction. The larger the crystallites, and the larger the particle size, the longer the time before dissolution of the hydrotalcite by attack of acid at the site of the hydroxide ions. Furthermore, it is believed that small particles are more readily dispersed through the meal. The buffering ability depends therefore both on the crystallite size and the particle size.
Tablet disintegration is another important factor for tablets containing antacids. Antacids are not intended to be absorbed into blood but rather act locally within the gastrointestinal tract and are dosed as an inorganic solid dose form. In these instances, tablet disintegration needs to provide the antacid particles with an increased surface area. The increased surface area is typically obtained by chewing the tablet.
Tabletting MgAl hydrotalcites significantly reduces their acid neutralization capacity and speed by the reduction in availability of particle surface area resulting from the tablet compression.
Consequently, hydrotalcites have been made commercially available only as chewable tablets or as liquid suspensions up to now. MgAl Hydrotalcites that are commercially available include Talcid Plus-tablets or -liquids, Ultacit, Talidat and Altacit Plus liquid.
Chewable tablets and liquid suspensions tend to have shorter residence times in the stomach than other dose forms such as non-chewable tablets. The duration of the antacid effect is very strongly dependent on the emptying rate of the stomach. Taken on an empty stomach, antacids tend to only neutralize acid for 30 to 60 minutes because the antacid quickly leaves the stomach whereas if taken with food, the protective effect may last as long as 2 or 3 hours. However, some antacids may not work in the presence of food because of drug-food interactions competing with its antacid functionality.
Hydrotalcite powders typically display poor flowability characteristics especially when in fine powder form; however, more coarse material results in inhibition of antacid performance (see Table 1). Powders of poor flowability are typically characterised as being cohesive, having a high Hausner ratio, moderate to high wall friction angles and a tendency to develop significant shear strength under compaction. Poor flowability properties result in difficulties in filling capsules or manufacturing tablets on an industrial scale especially when a high content of the hydrotalcite material is required in the dose-unit.
Chewable tablets of antacids may result in an unpleasant taste due to chalkiness, bitter or metallic taste, grittiness, dryness and astringent properties of these materials. Chewable tablets could result in dental problems and it is more difficult to taste-mask the active ingredient. Furthermore, patients do not chew tablets uniformly which could result in variation of the effectiveness of the antacid. Liquid suspensions have the disadvantage of storage and convenience and are less portable. In addition, these dose forms deliver the active ingredient more rapidly which in turn could increase the likelihood of the acid-rebound effect occurring.
It has been suggested to coat antacid tablets with a coating material which will not dissolve in the mouth but will dissolve in the stomach. However, many coatings dissolve in the intestine and not the stomach and thus deliver the antacid at the wrong site. Moreover, although a coating may be used which dissolves in the stomach, the rate of dissolution may not be fast enough to allow for sufficient neutralizing gastric acid time before the antacid is removed from the stomach by gastric emptying. However, if the dissolution is too fast then the initial gastric acid fluid pH may rise too rapidly thereby causing the so-called acid-rebound effect.
H2 receptor antagonists or proton pump inhibitors are capable of blocking the acid production of the stomach over a period of several hours. However, the risk of side-effects can be more severe as these drugs are distributed throughout the entire body via the blood. H2 receptor or proton pump inhibitors antagonist are therefore not generally able to replace the antacids which have a lower risk of side-effects.